In 1959, Murray filed a case on behalf of her son, William J. Murray, who was being forced to attend Bible readings in school and was being harassed by teachers and school administrators for refusing to participate.

The consolidated case, usually cited as Abington School District v. Schempp (although arguably Murray v. Curlett became the more famous of the two), was argued before the United States Supreme Court on February 27 and February 28, 1963.[5] In her opening statement, Madalyn Murray said, in part:

"Your petitioners are atheists and they define their beliefs as follows. An atheist loves his fellow man instead of god. An atheist believes that heaven is something for which we should work now – here on earth for all men together to enjoy. An atheist believes that he can get no help through prayer but that he must find in himself the inner conviction and strength to meet life, to grapple with it, to subdue it, and enjoy it. An atheist believes that only in a knowledge of himself and a knowledge of his fellow man can he find the understanding that will help to a life of fulfillment. He seeks to know himself and his fellow man rather than to know a god. An atheist believes that a hospital should be built instead of a church. An atheist believes that a deed must be done instead of a prayer said. An atheist strives for involvement in life and not escape into death. He wants disease conquered, poverty vanquished, war eliminated. He wants man to understand and love man. He wants an ethical way of life. He believes that we cannot rely on a god or channel action into prayer nor hope for an end of troubles in a hereafter. He believes that we are our brother's keepers and are keepers of our own lives; that we are responsible persons and the job is here and the time is now."

On August 27, 1995, Madalyn, Jon, and Robin O'Hair disappeared from the organization's former Austin, Texas headquarters, along with over $550,000 of the organization's funds. The three were abducted, robbed and murdered by ex-convict and former employee David Waters.[6][7]Ellen Johnson succeeded Madalyn O'Hair after her disappearance.[8]

In May 2007, ABC News featured a report on discrimination and bad treatment the Smalkowski family suffered from government officials in Hardesty, Oklahoma.[15] The report included information about an ongoing lawsuit, which was filed by American Atheists on behalf of the Smalkowski family. The lawsuit alleges the Hardesty Public School District violated Nicole Smalkowski's constitutional rights with bullying behavior, trumped-up charges, and suspension from the school basketball team.[15][16] Also in May, Joe Zamecki organized a local demonstration at the state capitol building in Austin, Texas, against the National Day of Prayer, in contrast to the official government creation, recognition, and status of the prayer events on the day.[17]

An announcement posted on the organization's blog on May 2, 2008 stated that Johnson was leaving the presidency of American Atheists for unspecified reasons. It was later revealed that her removal was not voluntary.[18] Frank Zindler was named acting president, followed by presidents Ed Buckner in September 2008, and Dave Silverman in September 2010.[19]

In November 2005, the Godless Americans Political Action Committee (GAPAC), an American PAC, was formed by American Atheists to endorse political candidates who support the separation of church and state.[20] Subsequently, atheists have become more outspoken about being an ignored voice in the United States.[21]

In May 2013 the American Atheists settled with Bradford County, Florida, regarding a monument containing the ten commandments. The American Atheists would be allowed to place their own monument onto public property. This marks the first time that such a monument will be placed on public land.[22] The monument is being furnished by American Atheists via a grant from the Stiefel Freethought Foundation.[23]

The American Atheists organization is known for its controversial antireligious billboards, intended by the organization to draw out closeted atheists within religious groups. A billboard on the Brooklyn-Queens Expressway displaying the Hebrew Tetragrammaton erected after the celebration of the Jewish holy day of Purim caused outrage from many Jews.[24] The same billboard was rejected by a landowner in an Orthodox Jewish neighborhood which drew a reaction from American Atheists' president David Silverman, who stated that this was a case of religious bigotry.[25][26] A satirical billboard depicting the Nativity during the Christmas season was also erected in 2010, causing a reaction from many American Christians, including the construction of a counter-billboard by the Catholic League.[27][28] A billboard in Paterson, New Jersey with the name of Allah in Arabic and the words "You know it’s a myth and you have a choice" drew criticism from local Muslims who "felt it was disrespectful and insulting but they agreed that the American Atheists have the right to put up their billboards where they want."[29]

On 29 July 2014, at a New York launch party, the group revealed an Internet television channel on the Roku streaming media platform, showing a 24-hour live stream of programming alongside an on-demand service. President of American Atheist, David Silverman, explained that the new channel would "...provide a breadth of content, from science to politics to comedy, all centered around our common freedom from religion."[30]AtheistTV became only the second atheist channel on Roku, but it is the first atheist channel with both live and on-demand video content. The platform hosts over 400 religious channels,[31] yet a few outspoken religious figures saw AtheistTV as a sign of intolerance towards Christianity.[32]

American Atheists Inc., Daniel Cooney, v. Bradford County, Florida (2012)[dead link][40] Filed suit over a display of the Ten Commandments on public property. Went to mediation. Resolved with a monument designed by American Atheists.

American Atheists v. Port Authority (2011) Filed suit against the placement of cross-shaped steel beams called the "World Trade Center Cross" at the National September 11 Memorial and Museum.[41] On March 28, 2013, United States District Court Judge Deborah Batts granted a motion of judgment in favor of the defendant. American Atheists stated at the time that they would appeal this decision.[42]